Expandable medical device for delivery of beneficial agent

ABSTRACT

An expandable medical device having a plurality of elongated struts, the plurality of elongated struts being joined together to form a substantially cylindrical device which is expandable from a cylinder having a first diameter to a cylinder having a second diameter, and the plurality of struts each having a strut width in a circumferential direction. At least one of the plurality of struts includes at least one opening extending at least partially through a thickness of said strut. A beneficial agent may be loaded into the opening within the strut. The expandable medical device may further include a plurality of ductile hinges formed between the elongated struts, the ductile hinges allowing the cylindrical device to be expanded or compressed from the first diameter to the second diameter by deformation of the ductile hinges.

CROSS-REFERENCE TO RELATED APPLICATIONS

Ser. No. 10/456,292, filed Jun. 5, 2003, which is a continuation of U.S.patent application Ser. No. 09/688,092, filed on Oct. 16, 2000, nowabandoned, each of which are incorporated herein by reference in theirentirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to tissue-supporting medical devices, andmore particularly to expandable, non-removable devices that areimplanted within a bodily lumen of a living animal or human to supportthe organ and maintain patency, and that can deliver a beneficial agentto the intervention site.

2. Summary of the Related Art

In the past, permanent or biodegradable devices have been developed forimplantation within a body passageway to maintain patency of thepassageway. These devices are typically introduced percutaneously, andtransported transluminally until positioned at a desired location. Thesedevices are then expanded either mechanically, such as by the expansionof a mandrel or balloon positioned inside the device, or expandthemselves by releasing stored energy upon actuation within the body.Once expanded within the lumen, these devices, called stents, becomeencapsulated within the body tissue and remain a permanent implant.

Known stent designs include monofilament wire coil stents (U.S. Pat. No.4,969,458); welded metal cages (U.S. Pat. Nos. 4,733,665 and 4,776,337);and, most prominently, thin-walled metal cylinders with axial slotsformed around the circumference (U.S. Pat. Nos. 4,733,665, 4,739,762,and 4,776,337). Known construction materials for use in stents includepolymers, organic fabrics and biocompatible metals, such as, stainlesssteel, gold, silver, tantalum, titanium, and shape memory alloys such asNitinol.

U.S. Pat. Nos. 4,733,665, 4,739,762, and 4,776,337 disclose expandableand deformable interluminal vascular grafts in the form of thin-walledtubular members with axial slots allowing the members to be expandedradially outwardly into contact with a body passageway. After insertion,the tubular members are mechanically expanded beyond their elastic limitand thus permanently fixed within the body. The force required to expandthese tubular stents is proportional to the thickness of the wallmaterial in a radial direction. To keep expansion forces withinacceptable levels for use within the body (e.g., 5-10 atm), thesedesigns must use very thin-walled materials (e.g., stainless steeltubing with 0.0025 inch thick walls). However, materials this thin arenot visible on conventional fluoroscopic and x-ray equipment and it istherefore difficult to place the stents accurately or to find andretrieve stents that subsequently become dislodged and lost in thecirculatory system.

Further, many of these thin-walled tubular stent designs employ networksof long, slender struts whose width in a circumferential direction istwo or more times greater than thickness in a radial direction. Whenexpanded, these struts are frequently unstable, that is, they display atendency to buckle, with individual struts twisting out of plane.Excessive protrusion of these twisted struts into the bloodstream hasbeen observed to increase turbulence, and thus encourage thrombosis.Additional procedures have often been required to attempt to correctthis problem of buckled struts. For example, after initial stentimplantation is determined to have caused buckling of struts, a second,high-pressure balloon (e.g., 12 to 18 atm) would be used to attempt todrive the twisted struts further into the lumen wall. These secondaryprocedures can be dangerous to the patient due to the risk of collateraldamage to the lumen wall.

Many of the known stents display a large elastic recovery, known in thefield as “recoil,” after expansion inside a lumen. Large recoilnecessitates over-expansion of the stent during implantation to achievethe desired final diameter. Over-expansion is potentially destructive tothe lumen tissue. Known stents of the type described above experiencerecoil of up to about 6 to 12% from maximum expansion.

Large recoil also makes it very difficult to securely crimp most knownstents onto delivery catheter balloons. As a result, slippage of stentson balloons during interlumenal transportation, final positioning, andimplantation has been an ongoing problem. Many ancillary stent securingdevices and techniques have been advanced to attempt to compensate forthis basic design problem. Some of the stent securing devices includecollars and sleeves used to secure the stent onto the balloon.

Another problem with known stem designs is non-uniformity in thegeometry of the expanded stent. Non-uniform expansion can lead tonon-uniform coverage of the lumen wall creating gaps in coverage andinadequate lumen support. Further, over expansion in some regions orcells of the stent can lead to excessive material strain and evenfailure of stent features. This problem is potentially worse in lowexpansion force stents having smaller feature widths and thicknesses inwhich manufacturing variations become proportionately more significant.In addition, a typical delivery catheter for use in expanding a stentincludes a balloon folded into a compact shape for catheter insertion.The balloon is expanded by fluid pressure to unfold the balloon anddeploy the stent. This process of unfolding the balloon causes unevenstresses to be applied to the stent during expansion of the balloon dueto the folds causing the problem non-uniform stent expansion.

U.S. Pat. No. 5,545,210 discloses a thin-walled tubular stentgeometrically similar to those discussed above, but constructed of anickel-titanium shape memory alloy (“Nitinol”). This design permits theuse of cylinders with thicker walls by making use of the lower yieldstress and lower elastic modulus of martensitic phase Nitinol alloys.The expansion force required to expand a Nitinol stent is less than thatof comparable thickness stainless steel stents of a conventional design.However, the “recoil” problem after expansion is significantly greaterwith Nitinol than with other materials. For example, recoil of a typicaldesign Nitinol stent is about 9%. Nitinol is also more expensive, andmore difficult to fabricate and machine than other stent materials, suchas stainless steel.

All of the above stents share a critical design property in each design,the features that undergo permanent deformation during stent expansionare prismatic, i.e., the cross sections of these features remainconstant or change very gradually along their entire active length. To afirst approximation, such features deform under transverse stress assimple beams with fixed or guided ends; essentially, the features act asa leaf springs. These leaf spring like structures are ideally suited toproviding large amounts of elastic deformation before permanentdeformation commences. This is exactly the opposite of ideal stealbehavior. Further, the force required to deflect prismatic stent strutsin the circumferential direction during stent expansion is proportionalto the square of the width of the strut in the circumferentialdirection. Expansion forces thus increase rapidly with strut width inthe above stent designs. Typical expansion pressures required to expandknown stents are between about 5 and 10 atmospheres. These forces cancause substantial damage to tissue if misapplied.

In addition to the above-mentioned risks to a patient, restenosis is amajor complication which can arise following the implantation of stents,using stent devices such as those described above, and other vascularinterventions such as angioplasty. Simply defined, restenosis is a woundhealing process that reduces the vessel lumen diameter by scar tissueformation and which may ultimately result in reocclusion of the lumen.Despite the introduction of improved surgical techniques, devices andpharmaceutical agents, the overall restenosis rate is still reported inthe range of 25% to 50% within six to twelve months after an angioplastyprocedure. To correct this problem, additional revascularizationprocedures are frequently required, thereby increasing trauma and riskto the patient.

Several techniques under development to address the problem ofrestenosis are irradiation of the injury site and the use of stents todeliver a variety of beneficial or pharmaceutical agents to thetraumatized vessel lumen. In the latter case, a stent is frequentlysurface-coated with a beneficial agent (often a drug-impregnatedpolymer) and implanted at the angioplasty site. Alternatively, anexternal drug-impregnated polymer sheath is mounted over the stent andco-deployed in the vessel. In either case, it has proven difficult todeliver a sufficient amount of beneficial agent to the trauma site so asto satisfactorily prevent the growth of scar tissue and thereby reducethe likelihood of restenosis. Even with relatively thick coatings of thebeneficial agent or sheaths of increased thickness surrounding thestents, restenosis has been found to occur. Furthermore, increasing theeffective stent thickness (e.g., by providing increased coatings of thebeneficial agent) is undesirable for a number of reasons, includingincreased trauma to the vessel lumen during implantation and reducedflow cross-section of the lumen after implantation. Moreover, coatingthickness is one of several factors that affect the release kinetics ofthe beneficial agent, and limitations on thickness thereby limit therange of release rates, durations, and the like that can be achieved.

SUMMARY OF THE INVENTION

In view of the drawbacks of the prior art, it would be advantageous toprovide a stent capable of delivering a relatively large volume of abeneficial agent to a traumatized site in a vessel lumen withoutincreasing the effective wall thickness of the stent, and withoutadversely impacting the mechanical expansion properties of the stent.

It would further be advantageous to have such a stent, which alsosignificantly increases the available depth of the beneficial agentreservoir.

It would be further advantageous to be able to expand such a stent withan expansion force at a low level independent of choice of stentmaterials, material thickness, or strut dimensions.

It would further be advantageous to have such a tissue-supporting devicethat permits a choice of material thickness that could be viewed easilyon conventional fluoroscopic equipment for any material.

It would also be advantageous to have such a tissue-supporting devicethat is inherently stable during expansion, thus eliminating bucklingand twisting of structural features during stent deployment.

In addition, it would be advantageous to have such a tissue-supportingdevice with minimal elastic recovery, or “recoil” of the device afterexpansion.

It would be advantageous to have such a tissue supporting device thatcan be securely crimped to the delivery catheter without requiringspecial tools, techniques, or ancillary clamping features.

In accordance with one aspect of the invention, an expandable medicaldevice includes a cylindrical tube, and a network of elongated strutsformed in the cylindrical tube, wherein each of the elongated struts areaxially displaced from adjacent struts. A plurality of ductile hingesare formed between the elongated struts. The ductile hinges allow thecylindrical tube to be expanded or compressed from a first diameter to asecond diameter by deformation of the ductile hinges. Further, at leastone of the elongated struts includes at least one opening for loading ofa beneficial agent therein. The at least one opening may include aplurality of openings that extend through a thickness of the at leastone strut, so as to thereby define a through-opening, or the openingsmay have a depth less than a thickness of the at least one strut, so asto thereby define a recess. A beneficial agent is loaded within the atleast one opening, wherein the beneficial agent includesantiproliferatives, antithrombins, large molecules, microspheres,biodegradable agents, or cells. The at least one opening of the at leastone strut forms a protected receptor for loading the beneficial agenttherein.

In accordance with a further aspect of the present invention, anexpandable medical device includes a plurality of elongated struts, theplurality of elongated struts joined together to form a substantiallycylindrical device which is expandable from a cylinder having a firstdiameter to a cylinder having a second diameter, and the plurality ofstruts each having a strut width in a circumferential direction. Atleast one of the plurality of struts includes at least one recessextending at least partially through a thickness of the strut. The atleast one recess may extend entirely through the thickness of the strutso as to define a through-opening and the at least one recess may begenerally rectangular or polygonal.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in greater detail with reference tothe preferred embodiments illustrated in the accompanying drawings, inwhich like elements bear like reference numerals, and wherein:

FIG. 1 is a perspective view of a tissue-supporting device in accordancewith a first preferred embodiment of the present invention;

FIG. 2 is an enlarged side view of a portion thereof;

FIG. 3 is an enlarged side view of a tissue-supporting device inaccordance with a further preferred embodiment of the present invention;

FIG. 4 is an enlarged side view of a portion of the stent shown in thedevice of FIG. 3;

FIG. 5 is an enlarged cross section of an opening thereof;

FIG. 6 is an enlarged cross section of an opening thereof illustratingbeneficial agent loaded into the opening;

FIG. 7 is an enlarged cross section of an opening thereof illustrating abeneficial agent loaded into the opening and a thin coating of abeneficial agent;

FIG. 8 is an enlarged cross section of an opening thereof illustrating abeneficial agent loaded into the opening and thin coatings of differentbeneficial agents on different surfaces of the device;

FIG. 9 is an enlarged side view of a portion of a stent in accordancewith yet another preferred embodiment of the present invention;

FIGS. 10 a-10 c are perspective, side, and cross-sectional views of anidealized ductile hinge for purposes of analysis, and FIG. 10 d is astress/strain curve for the idealized ductile hinge;

FIG. 11 is a perspective view of a simple beam for purposes ofcalculation;

FIG. 12 is a moment verses curvature graph for a rectangular beam; and

FIG. 13 is an enlarged side view of a bent ductile hinge.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to FIGS. 1 and 2, a tissue supporting device in accordancewith a preferred embodiment of the present invention is shown generallyby reference numeral 10. The tissue supporting device 10 includes aplurality of cylindrical tubes 12 connected by S-shaped bridgingelements 14. The bridging elements 14 allow the tissue supporting deviceto bend axially when passing through the tortuous path of thevasculature to the deployment site and allow the device to bend whennecessary to match the curvature of a lumen to be supported. TheS-shaped bridging elements 14 provide improved axial flexibility overprior art devices due to the thickness of the elements in the radialdirection which allows the width of the elements to be relatively smallwithout sacrificing radial strength. For example, the width of thebridging elements 14 may be about 0.0015-0.0018 inches (0.0381-0.0457mm). Each of the cylindrical tubes 12 has a plurality of axial slots 16extending from an end surface of the cylindrical tube toward an oppositeend surface.

Formed between the slots 16 is a network of axial struts 18 and links22. The cross section (and rectangular moment of inertia) of each of thestruts 18 is preferably not constant along the length of the strut.Rather, the strut cross section changes abruptly at both ends of eachstrut 18 adjoining the links 22. The preferred struts 18 are thus notprismatic. Each individual strut 18 is preferably linked to the rest ofthe structure through a pair of reduced sections 20, one at each end,which act as stress/strain concentration features. The reduced sections20 of the struts function as hinges in the cylindrical structure. Sincethe stress/strain concentration features are designed to operate intothe plastic deformation range of generally ductile materials, they arereferred to as ductile hinges 20. Such features are also commonlyreferred to as “Notch Hinges” or “Notch Springs” in ultra-precisionmechanism design, where they are used exclusively in the elastic range.

With reference to the drawings and the discussion, the width of anyfeature is defined as its dimension in the circumferential direction ofthe cylinder. The length of any feature is defined as its dimension inthe axial direction of the cylinder. The thickness of any feature isdefined as the wall thickness of the cylinder.

Ductile hinges 20 are preferably asymmetric ductile hinges that producedifferent strain versus deflection-angle functions in expansion andcompression. Each of the ductile hinges 20 is formed between a arcsurface 28 and a concave notch surface 29. The ductile hinge 20according to a preferred embodiment essentially takes the form of asmall, prismatic curved beam having a substantially constant crosssection. However, a thickness of the curved ductile hinge 20 may varysomewhat as long as the ductile hinge width remains constant along aportion of the hinge length. The width of the curved beam is measurealong the radius of curvature of the beam. This small curved beam isoriented such that the smaller concave notch surface 29 is placed intension in the device crimping direction, while the larger arc surface28 of the ductile hinges is placed in tension in the device expansiondirection. Again, there is no local minimum width of the ductile hinge20 along the (curved) ductile hinge axis, and no concentration ofmaterial strain. During device expansion tensile strain will bedistributed along the arc surface 28 of the hinge 20 and maximumexpansion will be limited by the angle of the wails of the concave notch29 which provide a geometric deflection limiting feature. The notches 29each have two opposed angled walls 30 which function as a stop to limitgeometric deflection of the ductile hinge, and thus limit maximum deviceexpansion. As the cylindrical tubes 12 are expanded and bending occursat the ductile hinges 20, the angled side walls 30 of the notches 29move toward each other. Once the opposite side walls 30 of a notch comeinto contact with each other, they resist further expansion of theparticular ductile hinge causing further expansion to occur at othersections of the tissue supporting device. This geometric deflectionlimiting feature is particularly useful where uneven expansion is causedby either variations in the tissue supporting device 10 due tomanufacturing tolerances or uneven balloon expansion. Maximum tensilestrain can therefore be reliably limited by adjusting the initial lengthof the arc shaped ductile hinge 20 over which the total elongation isdistributed.

The presence of the ductile hinges 20 allows all of the remainingfeatures in the tissue supporting device to be increased in width or thecircumferentially oriented component of their respective rectangularmoments of inertia—thus greatly increasing the strength and rigidity ofthese features. The net result is that elastic, and then plasticdeformation commence and propagate in the ductile hinges 20 before otherstructural elements of the device undergo any significant elasticdeformation. The force required to expand the tissue supporting device10 becomes a function of the geometry of the ductile hinges 20, ratherthan the device structure as a whole, and arbitrarily small expansionforces can be specified by changing hinge geometry for virtually anymaterial wall thickness. In particular, wall thicknesses great enough tobe visible on a fluoroscope can be chosen for any material of interest.

In order to get minimum recoil, the ductile hinges 20 should be designedto operate well into the plastic range of the material, and relativelyhigh local strain-curvatures are developed. When these conditions apply,elastic curvature is a very small fraction of plastic or totalcurvature, and thus when expansion forces are relaxed, the percentchange in hinge curvature is very small. When incorporated into a strutnetwork designed to take maximum advantage of this effect, the elasticspringback, or “recoil,” of the overall stem structure is minimized.

In the preferred embodiment of FIGS. 1 and 2, it is desirable toincrease the width of the individual struts 18 between the ductilehinges 20 to the maximum width that is geometrically possible for agiven diameter and a given number of struts arrayed around thatdiameter. The only geometric limitation on strut width is the minimumpractical width of the slots 16 which is about 0.002 inches (0.0508 mm)for laser machining. Lateral stiffness of the struts 18 increases as thecube of strut width, so that relatively small increases in strut widthsignificantly increase strut stiffness. The net result of insertingductile hinges 20 and increasing strut width is that the struts 18 nolonger act as flexible leaf springs, but act as essentially rigid beamsbetween the ductile hinges. All radial expansion or compression of thecylindrical tissue supporting device 10 is accommodated by mechanicalstrain in the hinge features 20, and yield in the hinge commences atvery small overall radial expansion or compression.

Yield in ductile hinges at very low gross radial deflections alsoprovides the superior crimping properties displayed by the ductilehinge-based designs. When a tissue supporting device is crimped onto afolded catheter balloon, very little radial compression of the device ispossible since the initial fit between balloon and device is alreadysnug. Most stents simply rebound elastically after such compression,resulting in very low clamping forces and the attendant tendency for thestent to slip on the balloon. Ductile hinges, however, sustainsignificant plastic deformation even at the low deflections occurringduring crimping onto the balloon, and therefore a device employingductile hinges displays much higher clamping forces. The ductile hingedesigns according to the present invention may be securely crimped ontoa balloon of a delivery catheter by hand or by machine without the needfor auxiliary retaining devices commonly used to hold known stents inplace.

The ductile hinge 20 illustrated in FIGS. 1 and 2 is exemplary of apreferred structure that will function as a stress/strain concentrator.Many other stress/strain concentrator configurations may also be used asthe ductile hinges in the present invention, as shown and described forexample in U.S. application Ser. No. 09/183,555, the entire contents ofwhich is hereby incorporated by reference. The geometric details of thestress/strain concentration features or ductile hinges 20 can be variedgreatly to tailor the exact mechanical expansion properties to thoserequired in a specific application. The ductile hinges according to thepresent invention generally include an abrupt change in width of a strutthat functions to concentrate stresses and strains in the narrowersection of the strut. These ductile hinges also generally includefeatures to limit mechanical deflection of attached struts and featuresto control material strain during large strut deflections. Although theductile hinges have been illustrated in FIG. 2 as positioned along thelength of the struts 18 and the links 22, they may also be positioned atother locations in other designs without departing from the presentinvention.

At intervals along the neutral axis of the struts 18, at least one andmore preferably a series of through-openings 24 are formed by laserdrilling or any other means known to one skilled in the art. Similarly,at least one and preferably a series of through-openings 26 are formedat selected locations in the links 22. Although the use ofthrough-openings 24 and 26 in both the struts 18 and links 22 ispreferred, it should be clear to one skilled in the art thatthrough-openings could be formed in only one of the struts and links. Inthe illustrated embodiment, the through-openings 24, 26 are circular innature and thereby form cylindrical holes extending through the width ofthe tissue supporting device 10. It should be apparent to one skilled inthe art, however, that through-openings of any geometrical shape orconfiguration could of course be used without departing from the scopeof the present invention.

The behavior of the struts 18 in bending is analogous to the behavior ofan I-beam or truss. The outer edge elements 32 of the struts 18correspond to the I-beam flange and carry the tensile and compressivestresses, whereas the inner elements 34 of the struts 18 correspond tothe web of an I-beam which carries the shear and helps to preventbuckling and wrinkling of the faces. Since most of the bending load iscarried by the outer edge elements 32 of the struts 18, a concentrationof as much material as possible away from the neutral axis results inthe most efficient sections for resisting strut flexure. As a result,material can be judiciously removed along the axis of the strut so as toform through-openings 24, 26 without adversely impacting the strengthand rigidity of the strut. Since the struts 18 and links 22 thus formedremain essentially rigid during stent expansion, the through-openings24, 26 are also non-deforming.

The term “agent” as used herein is intended to have its broadestpossible interpretation and is used to include any therapeutic agent ordrug, as well as any body analyte, such as glucose. The terms “drug” and“therapeutic agent” are used interchangeably to refer to anytherapeutically active substance that is delivered to a bodily lumen ofa living being to produce a desired, usually beneficial, effect. Thepresent invention is particularly well suited for the delivery ofantiproliferatives (antirestenosis agents) such as paclitaxel andrapamycin for example, and antithrombins such as heparin, for example.Additional uses, however, include therapeutic agents in all the majortherapeutic areas including, but not limited to anti-infectives such asantibiotics and antiviral agents; analgesics, including fentanyl,sufentanil, buprenorphine and analgesic combinations; anesthetics;anorexics; antiarthritics; antiasthmatic agents such as terbutaline;anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals;antihistamines; anti-inflammatory agents; antimigraine preparations;antimotion sickness preparations such as scopolamine and ondansetron;antinauseants; antineoplastics; antiparkinsonism drugs; antipruritics;antipsychotics; antipyretics; antispasmodics, including gastrointestinaland urinary; anticholinergics; syrnpathomimetrics; xanthine derivatives;cardiovascular preparations, including calcium channel blockers such asnifedipine; beta blockers; beta-agonists such as dobutamine andritodrine; antiarrythmics; antihypertensives such as atenolol; ACEinhibitors such as ranitidine; diuretics; vasodilators, includinggeneral, coronary, peripheral, and cerebral; central nervous systemstimulants; cough and cold preparations; decongestants; diagnostics;hormones such as parathyroid hormone; hypnotics; immunosuppressants;muscle relaxants; parasympatholytics; parasympathomimetrics;prostaglandins; proteins; peptides; psychostimulants; sedatives; andtranquilizers.

The through-openings 24, 26 may also be loaded with an agent, mostpreferably a beneficial agent, for delivery to the lumen in which thetissue support device 10 is deployed.

The term “agent” as used herein is intended to have its broadestpossible interpretation and is used to include any therapeutic agent ordrug, as well as any body analyte, such as glucose. The terms “drug” and“therapeutic agent” are used interchangeably to refer to anytherapeutically active substance that is delivered to a bodily lumen ofa living being to produce a desired, usually beneficial, effect. Thepresent invention is particularly well suited for the delivery ofantiproliferatives (antirestenosis agents) such as paclitaxil andrapamycin for example, and antithrombins such as heparin, for example.Additional uses, however, include therapeutic agents in all the majortherapeutic areas including, but not limited to: anti-infectives such asantibiotics and antiviral agents; analgesics, including fentanyl,sufentanil, buprenorphine and analgesic combinations; anesthetics;anorexics; antiarthritics; antiasthmatic agents such as terbutaline;anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals;antihistamines; anti-inflammatory agents; antimigraine preparations;antimotion sickness preparations such as scopolamine and ondansetron;antinauseants; antineoplastics; antiparkinsonism drugs; antipruritics;antipsychotics; antipyretics; antispasmodics, including gastrointestinaland urinary; anticholinergics; sympathomimetrics; xanthine derivatives;cardiovascular preparations, including calcium channel blockers such asnifedipine; beta blockers; beta-agonists such as dobutamine andritodrine; antiarrythrnics; antihypertensives such as atenolol; ACEinhibitors such as ranitidine; diuretics; vasodilators, includinggeneral, coronary, peripheral, and cerebral; central nervous systemstimulants; cough and cold preparations; decongestants; diagnostics;hormones such as parathyroid hormone; hypnotics; immunosuppressants;muscle relaxants; parasympatholytics; parasympathomimetrics;prostaglandins; proteins; peptides; psychostimulants; sedatives; andtranquilizers.

The openings form a protected receptor for loading beneficial agentsincluding large molecules, microspheres, beneficial agents within abiodegradable polymer carrier, and cells.

The embodiment of the invention shown in FIGS. 1 and 2 can be furtherrefined by using Finite Element Analysis and other techniques tooptimize the deployment of the beneficial agent within thethrough-openings of the struts and links. Basically, the shape andlocation of the through-openings 24, 26 can be modified to maximize thevolume of the voids while preserving the relatively high strength andrigidity of the struts 18 with respect to the ductile hinges 20.

FIG. 3 illustrates a further preferred embodiment of the presentinvention, wherein like reference numerals have been used to indicatelike components. The tissue supporting device 100 includes a pluralityof cylindrical tubes 12 connected by S-shaped bridging elements 14. Eachof the cylindrical tubes 12 has a plurality of axial slots 16 extendingfrom an end surface of the cylindrical tube toward an opposite endsurface. Formed between the slots 16 is a network of axial struts 18 andlinks 22. Each individual strut 18 is linked to the rest of thestructure through a pair of ductile hinges 20, one at each end, whichact as stress/strain concentration features. Each of the ductile hinges20 is formed between an arc surface 28 and a concave notch surface 29.The notches 29 each have two opposed angled walls 30 which function as astop to limit geometric deflection of the ductile hinge, and thus limitmaximum device expansion.

At intervals along the neutral axis of the struts 18, at least one andmore preferably a series of through-openings 24′ are formed by laserdrilling or any other means known to one skilled in the art. Similarly,at least one and preferably a series of through-openings 26′ are formedat selected locations in the links 22. Although the use ofthrough-openings 24′ and 26′ in both the struts 18 and links 22 ispreferred, it should be clear to one skilled in the art thatthrough-openings could be formed in only one of the struts and links. Inthe illustrated embodiment, the through-openings 24′ in the struts 18are generally rectangular whereas the through-openings 26′ in the links22 are polygonal. It should be apparent to one skilled in the art,however, that through-openings of any geometrical shape or configurationcould of course be used, and that the shape of through-openings 24, 24′may be the same or different from the shape of through-openings 26, 26′,without departing from the scope of the present invention. As describedin detail above, the through-openings 24′, 26′ may be loaded with anagent, most preferably a beneficial agent, for delivery to the lumen inwhich the tissue support device 100 is deployed.

The relatively large, protected through-openings 24, 24′, 26, 26′, asdescribed above, make the expandable medical device of the presentinvention particularly suitable for delivering agents having moreesoteric larger molecules or genetic or cellular agents, such as, forexample, protein/enzymes, antibodies, antisense, ribozymes, gene/vectorconstructs, and cells (including but not limited to cultures of apatient's own endothelial cells). Many of these types of agents arebiodegradable or fragile, have a very short or no shelf life, must beprepared at the time of use, or cannot be pre-loaded into deliverydevices such as stents during the manufacture thereof for some otherreason. The large through-openings in the expandable device of thepresent invention form protected areas or receptors to facilitate theloading of such an agent at the time of use, and to protect the agentfrom abrasion and extrusion during delivery and implantation.

FIG. 4 shows an enlarged view of one of the struts 18 of device 100disposed between a pair of ductile hinges 20. FIG. 5 illustrates a crosssection of one of the openings 24′ shown in FIG. 4. FIG. 6 illustratesthe same cross section when a beneficial agent 36 has been loaded intothe through-openings 24′ of the struts 18. Optionally, after loading thethrough-openings 24′ and/or the through-openings 26′ with a beneficialagent 36, the entire exterior surface of the stent can be coated with athin layer of a beneficial agent 38, which may be the same as ordifferent from the beneficial agent 36, as schematically shown in FIG.7. Still further, another variation of the present invention would coatthe outwardly facing surfaces of the stent with a first beneficial agent38 while coating the inwardly facing surfaces of the stent with adifferent beneficial agent 39, as illustrated in FIG. 8. The inwardlyfacing surface of the stent would be defined by at least the surfaces ofthe stent which, after expansion, forms the inner lumen passage. Theoutwardly facing surface of the stent would be defined by at least thesurface of the stent which, after expansion, is in contact with anddirectly supports the inner wall of the lumen.

FIG. 9 illustrates yet another preferred embodiment of the presentinvention, wherein like reference numerals have been used to indicatelike components. Unlike the stents 10, 100 described above, tissuesupporting device 200 does not include through-openings which extendthrough the entire width of the stent. Rather, the struts 18 and/orlinks 22 of stent 200 preferably include at least one and preferably aplurality of recesses 40, 442, formed respectively therein on one orboth side surfaces of the stent 200. The recesses 40, 42, also definedas openings, indentations, grooves, and the like, are sufficiently sizedso as to promote healing of the endothelial layer and to enable abeneficial agent 36 to be loaded therein. Recesses 40, 42, likethrough-holes 24, 24′, 26, 26′, may be formed in struts 18 withoutcompromising the strength and rigidity thereof for the same reasons asnoted above. As shown above in FIGS. 7 and 8, a surface coating of oneor more beneficial agents may also be provided on stent 200.

The tissue supporting device 10, 100, 200 according to the presentinvention may be formed of any ductile material, such as steel, gold,silver, tantalum, titanium, Nitinol, other shape memory alloys, othermetals, or even some plastics. One preferred method for making thetissue supporting device 10, 100, 200 involves forming a cylindricaltube 12 and then laser cutting the slots 16, notches 29 andthrough-openings 24, 24′, 26, 26′ or recesses 40, 42 into the tube.Alternatively, the tissue supporting device may be formed byelectromachining, chemical etching followed by rolling and welding, orany other method known to one skilled in the art.

The design and analysis of stress/strain concentration for ductilehinges, and stress/strain concentration features in general, is complex.The stress concentration factor can be calculated for simple ductilehinge geometries, but is generally useful only in the linear elasticrange. Stress concentration patterns for a number of other geometriescan be determined through photoelastic measurements and otherexperimental methods. Stent designs based on the use of stress/strainconcentration features, or ductile hinges, generally involve morecomplex hinge geometries and operate in the non-linear elastic andplastic deformation regimes.

The general nature of the relationship among applied forces, materialproperties, and ductile hinge geometry can be more easily understoodthrough analysis of an idealized hinge 60 as shown in FIGS. 10 a-10 c.The hinge 60 is a simple beam of rectangular cross section having awidth h, length L and thickness b. The idealized hinge 60 haselastic-ideally-plastic material properties which are characterized bythe ideal stress/strain curve of FIG. 10 d. It can be shown that the“plastic” or “ultimate bending moment” for such a beam is given by theexpression:

${M_{p} \equiv M_{ult}} = {\delta_{yp}\frac{{bh}^{2}}{4}}$

Where b corresponds to the cylindrical tube wall thickness, h is thecircumferential width of the ductile hinge, and δ_(yp) is the yieldstress of the hinge material. Assuming only that expansion pressure isproportional to the plastic moment, it can be seen that the requiredexpansion pressure to expand the tissue supporting device increaseslinearly with wall thickness b and as the square of ductile hinge widthh. It is thus possible to compensate for relatively large changes inwall thickness b with relatively small changes in hinge width h. Whilethe above idealized case is only approximate, empirical measurements ofexpansion forces for different hinge widths in several different ductilehinge geometries have confirmed the general form of this relationship.Accordingly, for different ductile hinge geometries it is possible toincrease the thickness of the tissue supporting device to achieveradiopacity while compensating for the increased thickness with a muchsmaller decrease in hinge width.

Ideally, the stent wall thickness b should be as thin as possible whilestill providing good visibility on a fluoroscope. For most stentmaterials, including stainless steel, this would suggest a thickness ofabout 0.005-0.007 inches (0.127-0.178 mm) or greater. The inclusion ofductile hinges in a stent design can lower expansion forces/pressures tovery low levels for any material thickness of interest. Thus ductilehinges allow the construction of optimal wall thickness tissuesupporting devices at expansion force levels significantly lower thancurrent non-visible designs.

The expansion forces required to expand the tissue supporting device 10,100, 200 according to the present invention from an initial conditionillustrated in FIG. 1 to an expanded condition is between 1 and 5atmospheres, preferably between 2 and 3 atmospheres. The expansion maybe performed in a known manner, such as by inflation of a balloon or bya mandrel. The tissue supporting device 10, 100, 200 in the expandedcondition has a diameter which is preferably up to three times thediameter of the device in the initial unexpanded condition.

Many tissue supporting devices fashioned from cylindrical tubes comprisenetworks of long, narrow, prismatic beams of essentially rectangularcross section as shown in FIG. 11. These beams which make up the knowntissue supporting devices may be straight or curved, depending on theparticular design. Known expandable tissue supporting devices have atypical wall thickness b of 0.0025 inches (0.0635 mm), and a typicalstmt width h of 0.005 to 0.006 inches (0.127-0.1524 mm). The ratio ofb:h for most known designs is 1:2 or lower. As b decreases and as thebeam length L increases, the beam is increasingly likely to respond toan applied bending moment M by buckling, and many designs of the priorart have displayed this behavior. This can be seen in the followingexpression for the “critical buckling moment” for the beam of FIG. 6.

$M_{crit} = \frac{\pi \; b^{3}h\sqrt{{EG}\left( {I - {0.63{b/h}}} \right.}}{6L}$Where: E = Modulus  of   Elasticity G = Shear  Modulus

By contrast, in a ductile hinge based design according to the presentinvention, only the hinge itself deforms during expansion. The typicalductile hinge 20 is not a long narrow beam as are the struts in theknown stents. Wall thickness of the present invention may be increasedto 0.005 inches (0.127 mm) or greater, while hinge width is typically0.002-0.003 inches (0.0508-0.0762 mm), preferably 0.0025 inches (0.0635min) or less. Typical hinge length, at 0.002 to 0.005 inches(0.0508-0.0127 mm), is more than an order of magnitude less than typicalstrut length. Thus, the ratio of b:h in a typical ductile hinge 20 is2:1 or greater. This is an inherently stable ratio, meaning that theplastic moment for such a ductile hinge beam is much lower than thecritical buckling moment M_(crit), and the ductile hinge beam deformsthrough normal strain-curvature. Ductile hinges 20 are thus notvulnerable to buckling when subjected to bending moments duringexpansion of the tissue supporting device 10, 100, 200.

To provide optimal recoil and crush-strength properties, it is desirableto design the ductile hinges so that relatively large strains, and thuslarge curvatures, are imparted to the hinge during expansion of thetissue supporting device. Curvature is defined as the reciprocal of theradius of curvature of the neutral axis of a beam in pure bending. Alarger curvature during expansion results in the elastic curvature ofthe hinge being a small fraction of the total hinge curvature. Thus, thegross elastic recoil of the tissue supporting device is a small fractionof the total change in circumference. It is generally possible to dothis because common stent materials, such as 316L-Stainless Steel havevery large elongations-to-failure (i.e., they are very ductile).

It is not practical to derive exact expressions for residual curvaturesfor complex hinge geometries and real materials (i.e., materials withnon-idealized stress/strain curves). The general nature of residualcurvatures and recoil of a ductile hinge may be understood by examiningthe moment-curvature relationship for the elastic-ideally-plasticrectangular hinge 60 shown in FIGS. 10 a-c. It may be shown that therelationship between the applied moment and the resulting beam curvatureis:

$M = {{M_{p}\left\lbrack {1 - {{1/3}\left( \frac{y_{o}}{h/2} \right)^{2}}} \right\rbrack} = {{3/2}\; {M_{yp}\left\lbrack {1 - {{1/3}\left( \frac{\kappa_{yp}}{\kappa} \right)^{2}}} \right\rbrack}}}$

This function is plotted in FIG. 12. It may be seen in this plot thatthe applied moment M asymptotically approaches a limiting value M_(P),called the plastic or ultimate moment. Beyond 31/12 M_(p) large plasticdeformations occur with little additional increase in applied moment.When the applied moment is removed, the beam rebounds elastically alonga line such as a-b. Thus, the elastic portion of the total curvatureapproaches a limit of 3/2 the curvature at the yield point. Theserelations may be expressed as follows:

$M_{p} = {\left. {\frac{3}{2}M_{yp}}\Rightarrow K_{rebound} \right. = {\frac{3}{2}K_{yp}}}$

Imparting additional curvature in the plastic zone cannot furtherincrease the elastic curvature, but will decrease the ratio of elasticto plastic curvature. Thus, additional curvature or larger expansion ofthe tissue supporting device will reduce the percentage recoil of theoverall stent structure.

As shown in FIG. 13, when a rigid strut 18 is linked to the ductilehinge 60 described above, the strut 18 forms an angle θ with thehorizontal that is a function of hinge curvature. A change in hingecurvature results in a corresponding change in this angle θ. The angularelastic rebound of the hinge is the change in angle Δθ that results fromthe rebound in elastic curvature described above, and thus angularrebound also approaches a limiting value as plastic deformationproceeds. The following expression gives the limiting value of angularelastic rebound for the idealized hinge of FIG. 13.

$\theta_{rebound} = {3ɛ_{yp}\frac{L}{h}}$

Where strain at the yield point is an independent material property(yield stress divided by elastic modulus); L is the length of theductile hinge; and h is the width of the hinge. For non-idealizedductile hinges made of real materials, the constant 3 in the aboveexpression is replaced by a slowly rising function of total strain, butthe effect of geometry would remain the same. Specifically, the elasticrebound angle of a ductile hinge decreases as the hinge width hincreases, and increases as the hinge length L increases, To minimizerecoil, therefore, hinge width h should be increased and length L shouldbe decreased.

Ductile hinge width h will generally be determined by expansion forcecriteria, so it is important to reduce hinge length to a practicalminimum in order to minimize elastic rebound. Empirical data on recoilfor ductile hinges of different lengths show significantly lower recoilfor shorter hinge lengths, in good agreement with the above analysis.

The ductile hinges 20 of the tissue supporting device 10, 100, 200provide a second important advantage in minimizing device recoil. Theembodiment of FIG. 1 shows a network of struts joined together throughductile hinges to form a cylinder. As the device is expanded, curvatureis imparted to the hinges 20, and the struts 18 assume an angle θ withrespect to their original orientation, as shown in FIG. 13. The totalcircumferential expansion of the tissue supporting device structure is afunction of hinge curvature (strut angle) and strut length. Moreover,the incremental contribution to stent expansion (or recoil) for anindividual strut depends on the instantaneous strut angle. Specifically,for an incremental change in strut angle Δθ, the incremental change incircumference ΔC will depend on the strut length R and the cosine of thestrut angle θ.

ΔC=RΔθ cos θ

Since elastic rebound of hinge curvature is nearly constant at any grosscurvature, the net contribution to circumferential recoil ΔC is lower athigher strut angles θ. The final device circumference is usuallyspecified as some fixed value, so decreasing overall strut length canincrease the final strut angle θ. Total stent recoil can thus beminimized with ductile hinges by using shorter struts and higher hingecurvatures when expanded.

Empirical measurements have shown that tissue supporting device designsbased on ductile hinges, such as the embodiment of FIG. 1, displaysuperior resistance to compressive forces once expanded despite theirvery low expansion force. This asymmetry between compressive andexpansion forces may be due to a combination of factors including thegeometry of the ductile hinge, the increased wall thickness, andincreased work hardening due to higher strain levels.

According to one example of the tissue supporting device of theinvention, the device can be expanded by application of an internalpressure of about 2 atmospheres or less, and once expanded to a diameterbetween 2 and 3 times the initial diameter can withstand a compressiveforce of about 16 to 20 gm/mm or greater. Examples of typicalcompression force values for prior art devices are 3.8 to 4.0 gm/mm.

While both recoil and crush strength properties of tissue supportingdevices can be improved by use of ductile hinges with large curvaturesin the expanded configuration, care must be taken not to exceed anacceptable maximum strain level for the material being used. Generally,ε_(max) is defined as maximum strain, and it is dependent on ductilehinge width h, ductile hinge length L, and bend angle θ in radians. Whenstrain, hinge width and bend angle are determined through othercriteria, an expression may be developed to determine the requiredlengths for the complicated ductile hinge geometry of the presentinvention. Typical values for the prismatic portions of the curvedductile hinges 20 range from about 0.002 to about 0.0035 inches(0.051-0.089 mm) in hinge width and about 0.002 to about 0.006 inches(0.051-0.152 mm) in hinge length.

In many designs of the prior art, circumferential expansion wasaccompanied by a significant contraction of the axial length of thestent which may be up to 15% of the initial device length. Excessiveaxial contraction can cause a number of problems in device deploymentand performance including difficulty in proper placement and tissuedamage. Designs based on ductile hinges 20 can minimize the axialcontraction, or foreshortening, of a tissue supporting device duringexpansion, as discussed in greater detail in the afore-mentioned U.S.application Ser. No. 09/183,555. This ability to control axialcontraction based on hinge and strut design provides great designflexibility when using ductile hinges. For example, a stent could bedesigned with zero axial contraction.

The stent 10, 100, 200 of the present invention illustrates the tradeoff between crush strength and axial contraction. Referring to FIG. 3, aportion of the tissue supporting device 100 having an array of struts 18and ductile hinges 20 are shown in the unexpanded state. The struts 18are positioned initially at an angle θ₁ with respect to a longitudinalaxis X of the device, As the device is expanded radially from theunexpanded state illustrated in FIG. 3, the angle θ₁ increases. In thiscase the device contracts axially from the onset of vertical expansionthroughout the expansion. A higher final strut angle θ₁, cansignificantly increase crush strength and decrease circumferentialrecoil of the stent structure. However, there is a trade off betweenincreased crush strength and increase in axial contraction.

According to one example of the present invention, the struts 18 arepositioned initially at an angle of about 0° to 45° with respect to alongitudinal axis of the device. As the device is expanded radially fromthe unexpanded state illustrated in FIG. 3, the strut angle increases toabout 20° to 80°.

In addition, while ductile hinges 20 are the preferred configuration forthe expandable medical device of the present invention, a stent withoutthe defined ductile hinges would also be included within the scope ofthe present invention.

While the invention has been described in detail with reference to thepreferred embodiments thereof, it will be apparent to one skilled in theart that various changes and modifications can be made and equivalentsemployed, without departing from the present invention.

1-20. (canceled)
 21. An expandable medical device comprising: a networkof elongated struts, each elongated strut having a neutral axis, innerand outer surfaces defining a thickness, and at least one substantiallyconstant-cross-section through-opening in the thickness at intervalsalong the neutral axis; a hinge having a reduced section formed ateither end of the elongated strut permitting the expandable medicaldevice to expand from a first diameter to a second diameter by firstelastically and then plastically deforming; and a beneficial agentcontained primarily within the through-openings, wherein the inner andouter surfaces of the struts are substantially without beneficial agentthereon and the struts are configured to substantially not deform duringthe expansion from the first diameter to the second diameter.
 22. Thedevice according to claim 21, wherein the through-openings are formed bylaser drilling.
 23. The device according to claim 21, wherein thenetwork of elongated struts form a cylindrical tube.
 24. The deviceaccording to claim 23, wherein at least two cylindrical tubes areconnected by S-shaped bridging elements.
 25. The device according toclaim 21, wherein the beneficial agent includes at least oneantiproliferative.
 26. The device according to claim 21, wherein thebeneficial agent is paclitaxel.
 27. The device according to claim 21,wherein the beneficial agent is a rapamycin.
 28. The device according toclaim 21, wherein a width of the hinge is defined as the dimension inthe direction perpendicular to a length of the hinge, a thickness of thehinge is defined as the dimension in the radial direction of the device,and the reduced section has a portion of constant width.
 29. The deviceaccording to claim 28, wherein a transition from the elongated strut tothe reduced section of the hinge is abrupt.
 30. The device according toclaim 21, wherein the beneficial agent includes antithrombins.